Hyperthyroidism is the most common hormone abnormality in felines. It is most common in older felines, and somewhat more common in females than in males. Hyperthyroidism is caused by overproduction of thyroid hormones, particularly thyroxine or T-4. Overproduction of T-4 can dramatically increase the animal's basal metabolic rate, leading to weight loss, increased appetite, restlessness, poor hair coat, tachycardia, increased drinking and urination, vomiting, diarrhea, panting, difficulty breathing, fever, elevated blood pressure, and eventually weakness, listlessness, muscle tremors, wasting, and death. Advanced hyperthyroidism is often associated with kidney problems and heart problems. Effective treatments include use of drugs such as methimazole or carbimazole, which inhibit production of thyroid hormones, radioiodine therapy, which destroys overactive thyroid cells, and surgical thyroidectomy. If the disease is detected too late, however, the damage may be irreversible. Accordingly, early diagnosis is critical.
The most common test for diagnosing hyperthyroidism is a blood test for T-4, where significantly elevated T-4 levels indicate hyperthyroidism, or a T-3 suppression test, which measures suppression of T-4 in response to administration of T-3, wherein absence of suppression indicate a hyperthyroid condition. However, a feline's level of T-3 and T-4 may fluctuate in the course of the day, rendering tests unreliable, and there are also various diseases that can artificially lower T-4 levels, thus masking a hyperthyroid condition. Radioimaging of the thyroid using technetium is possible, and may be useful to detect tumors or abnormal thyroid tissues, but it is expensive.
Accordingly, there is a need for alternative efficient and effective methods of detecting hyperthyroidism in felines.
A number of methods have been developed for studying differential gene expression, e.g., DNA microarrays, expressed tag sequencing (EST), serial analysis of gene expression (SAGE), subtractive hybridization, subtractive cloning and differential display (DD) for mRNA, RNA-arbitrarily primed PCR (RAP-PCR), real-time PCR (RT-PCR), representational difference analysis (RDA), two-dimensional gel electrophoresis, mass spectrometry, and protein microarray based antibody-binding for proteins.
Due to the complexity of the biological pathways implicated in hyperthyroidism and the inherent molecular interactions and intercellular signaling processes, it is highly desirable to understand at a genetic level the interactions that are taking place. Detection of dysregulated genes in the early stages of hyperthyroidism in felines is helpful in understanding the biology of hyperthyroidism in felines on a genome-wide basis, which would be helpful in designing methods for determining the risk of developing, predisposition for, diagnosing of, and devising and monitoring a treatment plan for hyperthyroidism.
A more detailed understanding of the biological pathways involved through gene expression profiling would aid in the development of diagnostic procedures, reagents and test kits as well as salutary pharmaceutical, nutraceutical and nutritional (dietary) interventions in the disease pathways. These approaches may enable early detection and potentially prevention or treatment of the underlying disorder. Dysregulated genes involved in the pathology of thyroid disorders may serve as important biomarkers for diagnosis and potentially prevention or treatment of the disorder and to optimize selection of appropriate pharmaceutical, nutraceutical and nutritional (dietary) interventions.
The level of gene expression and/or the determination of the level of functioning of an expressed gene product in a feline may be used to select an appropriate agent for therapeutic or prophylactic use. This data may be employed by the skilled worker in selecting appropriate drugs as agents for the prevention or treatment of renal diseases in felines through gene expression profiling. Gene expression data and analysis may also be used to select nutritional compositions, dietary supplements, and nutraceuticals having a salutary effect on promoting normal thyroid function performance by utilizing biomarkers indicative of a healthy state of kidney functioning.
Only very limited work has been done to date in screening the feline genome for gene expression profiles in connection with the diagnosis of diseases in felines. Studies in healthy populations of felines versus populations having a disease such as hyperthyroidism as described in this specification have not been extensively conducted. Little data is available with respect to the expression profile of the feline genome, especially with respect to the development of renal diseases in felines over time.
Hyperthyroidism is a leading cause of death in felines. To effectively treat hyperthyroidism, early diagnosis and treatment is essential, before there is irreversible damage to the heart and/or kidneys. Accordingly, there is a need for better methods to identify animals having hyperthyroidism or at elevated risk for hyperthyroidism, so that they can be treated appropriately.